Imaging of the buffering effect of insulin antibodies in the autoimmune hypoglycemic syndrome.
Insulin autoimmune hypoglycemia is characterized by recurrent hypoglycemia and high levels of immunoreactive insulin in the presence of insulin autoantibodies. The mechanisms inducing hypoglycemia are largely unknown. An [123I]insulin scintigraphic scanning was performed to directly demonstrate the effect of antibodies on insulin biodistribution in one patient with this syndrome both before and after treatment. The patient had insulin autoantibodies IgG3 lambda, which had a single site dissociation constant (Kd = 10(-7) mol/L, by Scatchard analysis), a very fast dissociation rate of immune complexes, and a very rapid association of [125I]insulin. Insulin receptors on red blood cells were down-regulated. The [123I]insulin scintigraphic study imaged the buffering effect of antibodies on insulin bioavailability. [123I]Insulin was not removed from the blood, and no liver or kidney uptake of the hormone occurred. The frequency and severity of hypoglycemic episodes required treatment. Insulin antibody levels decreased and [123I]insulin biodistribution improved after treatment with plasmapheresis and prednisone. Improved hormone bioavailability was further evidenced by the reduction in the hypoglycemic delay after i.v. insulin from 90 min before any treatment to 60 min after plasmapheresis and 30 min after steroid administration. Glucose tolerance was normal after treatment. Plasmapheresis followed by steroid treatment can lower the insulin antibody concentration, abolish severe hypoglycemia, and improve insulin biodistribution and glucose tolerance in insulin autoimmune hypoglycemia.
Dozio
N
N
Department of Medicine I, San Raffaele Scientific Institute, University of Milan, Italy. @dozion at imihsra.hsr.it
Scavini
M
M
Beretta
A
A
Sarugeri
E
E
Sartori
S
S
Belloni
C
C
Dosio
F
F
Savi
A
A
Fazio
F
F
Sodoyez
J C
JC
Pozza
G
G
D001323:Autoantibodies / Q000097:blood / Q000494:pharmacology*; D001327:Autoimmune Diseases; D001682:Biological Availability; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007003:Hypoglycemia / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy; D007074:Immunoglobulin G / Q000097:blood; D007328:Insulin / Q000097:blood / Q000276:immunology*; D007457:Iodine Radioisotopes; D008875:Middle Aged; D010956:Plasmapheresis; D011241:Prednisone / Q000627:therapeutic use; D011877:Radionuclide Imaging; D011972:Receptor, Insulin / Q000097:blood; D013577:Syndrome
D001323:Autoantibodies; D007074:Immunoglobulin G; D007328:Insulin; D007457:Iodine Radioisotopes; D011972:Receptor, Insulin; D011241:Prednisone